The identification of potentially important drugs often requires the measurement of the effect of these drugs on the transport of ions through membranes. For example, some drugs have produced life-threatening toxicity, associated with a delay in cardiac re-polarization or QT interval prolongation related to ion movement. For example, several drugs were recently withdrawn from the market because of their effect on the cell membrane transport system.
Ion channels are ubiquitous pore-forming proteins that allow the transport of ions across cell membranes. Ion channels facilitate the movement of a particular ionic species (for example, Na+,K+, Ca2+, Cr31 ) between cellular compartments and/or across the outer cell membrane with varying ion selectivity. Ion channels are dynamic structures which respond to external factors such as voltage gradients, ligands and mechanical forces. The pharmaceutical industry developed therapeutics that modify ion channel function. Examples include the anti-epileptics such as the sodium channel blocker carbamazepine, the antihypertensive dihydropyridine calcium channel blockers (NORVASC™, which is described by the trademark owner as a “PHARMACEUTICAL PREPARATION HAVING ANTIANGINAL AND ANTIHYPERTENSIVE PROPERTIES” and sulphonylurea potassium channel openers for diabetes (AMARYL™), which is described by the trademark owner as a “pharmaceutical preparation for use in the oral treatment of diabetes”. Recent total annual sales of ion channel targeted drugs are around $20 billion.
Ion channels are difficult molecular targets for drug development. Difficulties arises from the lack of suitable high throughput screening assay formats, the complexity of ion channel biophysics, and the range of potential binding sites and binding modes for drugs.
There remains a need for simpler methods for measuring transport rates of ions through a membrane.
Therefore, an object of the present invention is to provide a method and apparatus for measuring the transport rates of ions through membranes.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.